This project is a multidisciplinary approach to the problem of acute respiratory failure due to diffuse alveolar damage. Inflammatory mechanisms may initiate lung injury in some circumstances or may become activated by lung injury in others, thus serving to potentiate injury begun by other processes. We will examine the roles of complement and neutrophils in each of these circumstances using the technique of bronchoalveolar lavage to sample the alveolar milieu. Connective tissue accumulation occurs rapidly in the lungs of some patients with diffuse alveolar damage and probably contributes to the high mortality of the syndrome. We are analyzing connective tissue responses of humans and experimental animals with a variety of lung injuries, some of which lead to fibrosis and some which do not to define factors which are important determinants of connective tissue accumulation. Atelectasis is a common feature of diffuse alveolar damage but its role in the evaluation of the injury is not clear. We are investigating the changes in the lung's microvasculature in atelectasis using electron microscopy and various tracer molecules. Bacterial infection of the lung is a common complication of acute respiratory failure which contributes significantly to the morbidity of the syndrome. We are investigating the mechanisms whereby pathogenic bacteria are able to colonize the respiratory tract. The effects of bacterial products on lung cells in vivo and in vitro are being studied.